摘要
目的:通过观察血管紧张素Ⅱ受体拮抗剂(Angiotensin receptor blocker,ARB)对肾性高血压大鼠脑缺血再灌注后脑组织中基质金属蛋白酶-2(Matrix metalloproteinase-2,MMP-2)和基质金属蛋白酶-9(Matrix metalloproteinase-9,MMP-9)表达的影响,探讨ARB的脑保护机制。方法:将Wistar雄性大鼠32只随机分为高血压组和正常血压组。前组采用狭窄肾动脉方法建立肾性高血压大鼠模型,再随机分为高血压缺血再灌注组(Hypertension ischemic reperfusion,HIR)和HIR缬沙坦组(G),分别采用生理盐水和缬沙坦12mg/kg进行灌胃治疗4周;正常血压组分为假手术组(N)和缺血再灌注组(Ischemic reperfusion,IR),分别行假手术和缺血再灌注处理。采用大脑中动脉线栓法造成大脑缺血再灌注模型,缺血时间为2 h,再灌注22 h。采用免疫组织化学技术检测脑组织MMP-2和MMP-9的表达,用图象分析仪测定灰度值。结果:与N组比较,IR组MMP-2、MMP-9灰度值明显增高(P<0.01);与IR组比较,HIR组MMP-2、MMP-9灰度值增高(P<0.05);与HIR组比较,G组MMP-2、MMP-9灰度值减少(P<0.01)。结论:高血压加重缺血再灌注后脑组织MMP-2和MMP-9的表达;ARB能明显抑制脑组织MMP-2和MMP-9的表达。
Objective： To explore the mechanisms of angiotensin Ⅱ receptor antagonist（ARB ） -induced brain protection by investigating the effect of ARB on the expression of metalloproteinase-2 （MMP-2） and matrix metalloproteinasc-9 （MMP-9） in the brain of renal hypertensive rats after cerebral ischemia-reperfusion. Methods： Thirty-two male Wistar rats were randomly divided into a hypertensive group and a normal blood pressure group. Hypertension was produced by renal artery occlusion. The rats in the renal hypertensive group were randomly sub-divided into an ischemia-reperfusion （hypertension ischemic reperfusion HIR） group treated with normal saline and a HIR valsartan （G） group treated with valsartan （12 mg/kg per day） by gavage for 4 weeks. The normal blood pressure group was sub-divided into a sham operated group （N） and ischemia-reperfusion group （IR）. Cerebral ischemia was induced by middle cerebral artery occlusion with suture for 2 hours followed by 22 hours of reperfusion. The expression of MMP-2 and MMP-9 in brain tissue was detected by immunohistochemistry and their gray values were measured using image analysis. Results： The gray values of MMP-2 and MMP-9 in the IR group were significantly higher than those in the N group （P 〈0.01 ）. The gray values of MMP-2 and MMP-9 in the HIR group were significantly increased when compared with that in the IR group （P 〈0.05 ）. The gray values of MMP-2 and MMP-9 in the G group were reduced when compared with that in the HIR group （P〈0.01）. Conclusion： Hypertension aggravates ischemiareperfusion-induced expression of MMP-2 and MMP-9 in brain tissue. The increased expression of MMP-2 and MMP-9 in brain tissue can be inhibited by angiotensin n receptor antagonist.
出处
《重庆医科大学学报》
CAS
CSCD
北大核心
2010年第2期183-186,共4页
Journal of Chongqing Medical University
基金
贵州省遵义市科技局资助项目(编号:遵义市科合社字(2006)11号)
